Opioids are any endogenous or exogenous compounds that bind to an opioid receptor. Opioid receptors are localized primarily in the brain, spinal cord, and gastrointestinal tract. When opioids bind to their receptors in the brain and spinal cord they block pain transmission signals from the periphery of the body. Although opioids are very effective for moderate to severe pain, there are many well known problems associated with opioid therapy. Those problems include serious side effects such as cognitive dysfunction, respiratory depression, nausea/vomiting, urinary retention, and constipation. Further, chronic opioid therapy often results in the development of tolerance to the analgesic effect, resulting in dose escalation, as well as physical and psychological dependence.
Nornicotine, the primary metabolite of nicotine, binds to nicotinic receptors which are located in the brain, spinal cord and periphery (autonomic ganglia and smooth muscle). It has recently been appreciated that nicotinic receptor binding can also modulate pain signals to the brain suggesting their potential use in the treatment of pain (acute, chronic, cancer-related).
There is a great need for analgesic medications able to provide high efficacy pain relief while providing more favorable pharmacokinetics and reducing the possibility of undesirable effects. Enhancement of the analgesic effect of opioids as well as nornicotine has been described in the art Therefore, there is a need for a way to administer opioids and nornicotine to provide a more favorable pharmacokinetic profile.